Bone is a vascularized tissue composed of a cellular and an extra-cellular compartment, the latter of which predominates in terms of volume. Accordingly, bone metabolism is integrally related to the remainder of the body through the vascularization extending therethrough. Osteoblasts and osteoclasts are the major differentiated cells of bone. Most of the non-collagenous proteins of bone, such as bone sialoprotein (SP II), osteopontin and osteonectin have been shown to be synthesized by osteoblast-like cells in culture.
It is generally believed that acidic non-collagenous proteins of bone play a direct role in the processes of cell recruitment and mineralization which occur during coupled resorptive and formative phases of bone turnover.
Applicant has recently isolated a new non-collagenous phosphoprotein from the mineralized phase of rat calvarial tissue, bone acidic glycoprotein-75, referred to as BAG-75. Partial characterization of the glycoprotein revealed a distinctive N-terminal sequence, an Asx and Glx content of 29%, and the presence of 7% (w/w) organic phosphate. Ion exchange chromatography of the 4M guanidine HCl/0.5 MEDTA extracts of rat calvaria show that BAG-75 copurifies with small bone proteoglycans. This confirms the very acidic character of the glycoprotein. Although exhibiting nonidentical amino acid compositions, BAG-75 was found to share a limited sequence homology with osteopontin.
Other non-collagenous proteins have recently been studied. Studies have been conducted on osteocalcin, osteonectin, SP II, phosphoproteins, and osteopontin as possible regulators of de novo calcium hydroxyapatite formation and of crystal growth. The specific role of these individual non-collagenous proteins in bone matrix deposition and mineralization remains uncertain, possibly due to the existence of redundant, compensating factors.
The present invention relates to the discovery of detectable BAG-75 antigen in serum and very likely in synovial fluid. An immunoassay is carried out on blood serum using antibodies which selectively bind to BAG-75 or its 50,000 molecular weight fragment.